The National Institute of Health and Care Excellence (NICE) appraises the clinical and economic impact of health technologies to inform public reimbursement decision-making in England and Wales. Cost-effectiveness is the key criterion for informing recommendations. In April 2016, the Cancer Drugs Fund (CDF) was reformed to enable temporary reimbursement for oncology therapies where uncertainty exists, to collect real world evidence to inform subsequent NICE appraisals. In October 2016, osimertinib become the first drug to enter the newly-reformed CDF and 10 therapies have entered the CDF to 11/24/2017. Outside of oncology, three drugs (all orphan drugs appraised under the HST pathway) have been reimbursed under Managed Access Agreements (MAAs). Under MAAs, drugs are provided at a substantial discount while evidence generation activities are ongoing to inform future NICE appraisals. The first MAA was agreed in November 2015 for elosulfase alfa in Morquio A Syndrome with a second MAA in July 2016 for ataluren in Duchenne muscular dystrophy. Under a NICE consultation document published in October 2017 (on changes to increase technology appraisal process capacity), this ‘third option’ of temporary reimbursement under the CDF or an MAA was formally itemized for health technologies appraised via the single technology appraisal process, suggesting that these approaches may become more frequent in the future. As new technologies with transformational benefits are being developed for patients with severe unmet needs (e.g. CAR-T cell, gene therapies, and immuno-oncology), regulators are increasingly approving these at earlier stages of their clinical development process. This poses a challenge for reimbursement decision-makers who have to justify investment of limited economic resources for these high-cost therapies when significant uncertainty remains. Temporary reimbursement at a confidentially discounted level until the data package matures to inform a final reimbursement decision may represent a best-practice solution with applicability internationally.